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Driver mutations of cancer epigenomes

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Protein & Cell 2014年第4期5卷 265-296页

作者： David m. Roy Logan A. Walsh timothy A. Chan Human Oncology and Pathogenesis Program Memorial Sloan-Kettering Cancer Center New York NY 10065 USA Weill Cornell/Rockefeller/Sloan-Kettering Tri-lnstitutional mD-PhD Program New York NY 10065 USA Department of Radiation Oncology Memorial Sloan-Kettering Cancer Center New York NY 10065 USA

Epigenetic alterations are associated with all aspects of cancer, from tumor initiation to cancer progression and metastasis. It is now well understood that both losses and gains of DNA methylation as well as altered chro- matin organization contribute significantly to cancer- associated phenotypes. more recently, new sequencing technologies have allowed the identification of driver mutations in epigenetic regulators, providing a mecha- nistic link between the cancer epigenome and genetic alterations. Oncogenic activating mutations are now known to occur in a number of epigenetic modifiers （i.e. IDHll2, EZH2, DNmT3A）, pinpointing epigenetic path- ways that are involved in tumorigenesis. Similarly, investigations into the role of inactivating mutations in chromatin modifiers （i.e. KDm6A, CREBBPIEP300, SmARCB1） implicate many of these genes as tumor suppressors. Intriguingly, a number of neoplasms are defined by a plethora of mutations in epigenetic regu- lators, including renal, bladder, and adenoid cystic car- cinomas. Particularly striking is the discovery of frequent histone H3.3 mutations in pediatric glioma, a particularly aggressive neoplasm that has long remained poorly understood. Cancer epigenetics is a relatively new, promising frontier with much potential for improving cancer outcomes. Already, therapies such as 5-azacytidine and decitabine have proven that targeting epigenetic alterations in cancer can lead to tangible benefits. Understanding how genetic alterations give rise to the cancer epigenome will offer new possibilities for developing better prognostic and therapeutic strategies.

关键词： chromatin cancer epigenetics mutations,methylation

Ribozymes and the mechanisms that underlie RNA catalysis

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Frontiers of Chemical Science and Engineering 2016年第2期10卷 178-185页

作者： timothy J. Wilson Yijin Liu David m. J. Lilley Cancer Research UK Nucleic Acid Structure Research Group MSI/WTB Complex The University of Dundee Dundee DD1 5EH UK

Ribozymes are widespread, and catalyze some extremely important reactions in the cell. mechanistically most fall into one of two classes, using either metal ions or general acid-base catalysis. The nucleolytic ribozymes fall into the latter class, mostly using nucleobases. A sub-set of these use a combination of guanine base plus adenine acid to catalyze the cleavage reaction. New ribozymes are still being discovered at regular intervals and we can speculate on the potential existence of ribozymes that catalyze chemistry beyond phosphoryl transfer reactions, perhaps using small-molecule coenzymes.

关键词： RNA catalysis RNA structure catalytic mechanism

Geological Evidence for the Operation of Plate Tectonics throughout the Archean:Records from Archean Paleo-Plate Boundaries

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Journal of Earth Science 2018年第6期29卷 1291-1303页

作者： timothy m.Kusky Brian F.Windley Ali Polat State Key Laboratory for Geological Processes and mineral Resources China University of Geosciences Center for Global Tectonics School of Earth SciencesChina University of Geosciences Department of Geology University of Leicester Department of Earth and Environmental Sciences University of Windsor

Plate tectonics describes the horizontal motion of rigid lithospheric plates away from midoceanic ridges and parallel to transforms, towards deep-sea trenches, where the oceanic lithosphere is subducted into the mantle. This process is the surface expression of modern-day heat loss from Earth. One of the biggest questions in Geosciences today is ＂when did plate tectonics begin on Earth＂ with a wide range of theories based on an equally diverse set of constraints from geology, geochemistry, numerical modeling, or pure speculation. In this contribution, we turn the coin over and ask ＂when was the last appearance in the geological record for which there is proof that plate tectonics did not operate on the planet as it does today＂. We apply the laws of uniformitarianism to the rock record to ask how far back in time is the geologic record consistent with presently-operating kinematics of plate motion, before which some other mechanisms of planetary heat loss may have been in operation. Some have suggested that evidence shows that there was no plate tectonics before 800 ma ago, others sometime before 1.8–2.7 Ga, or before 2.7 Ga. Still others recognize evidence for plate tectonics as early as 3.0 Ga, 3.3–3.5 Ga, the age of the oldest rocks, or in the Hadean before 4.3 Ga. A key undiscussed question is： why is there such a diversity of opinion about the age at which plate tectonics can be shown to not have operated, and what criteria are the different research groups using to define plate tectonics, and to recognize evidence of plate tectonics in very old rocks？ Here, we present and evaluate data from the rock record, constrained by relevant geochemical-isotopic data, and conclude that the evidence shows indubitably that plate tectonics has been operating at least since the formation of the oldest rocks, albeit with some differences in processes, compositions, and products in earlier times of higher heat generation and mantle temperature, weaker oceanic lithosphere, hotte

关键词： Archean tectonics ophiolite OPS(oceanic plate stratigraphy) orogeny

New Research Progress on the Pre-Sinian Tectonic Evolution and Neotectonics of the Huangling Anticline Region,South China

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Journal of Earth Science 2012年第5期23卷 639-647页

作者：彭松柏 timothy m Kusky 周汉文王璐项伟 Three Gorges Research Center for Geo-hazard Ministry of EducationChina University of Geosciences Faculty of Earth Sciences China University of Geosciences Three Gorges Research Center for Geo-hazard Ministry of EducationChina University of Geosciences State Key Laboratory of Geological Processes and mineral Resources China University of Geosciences Faculty of Engineering China University of Geosciences

In this paper the authors briefly introduce and review the new progress of the newly dis-covered Proterozoic miaowan （庙湾） ophiolite and Neoproterozoic HuangUng （黄陵） granitoids in the southern Huangling anticline in the Yangtze craton, and the tectonic evolution significance of assemblage and breakup of Rodinia and Columbia supereontinent in South China.

关键词： Yangtze craton South China,HuanglingRodinia andanticline Proterozoic ophiolite,Columbia supercontinent.

Neoadjuvant chemotherapy for colorectal liver metastases:A contemporary review of the literature

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World Journal of Gastrointestinal Oncology 2021年第9期13卷 1043-1061页

作者： marissa Guo Ning Jin timothy Pawlik Jordan m Cloyd Department of Surgery The Ohio State University Medical CenterColumbusOH 43210United States Department of Internal medicine Division of Medical OncologyThe Ohio State University Medical CenterColumbusOH 43210United States Department of Surgery The Ohio State UniversityColumbusOH 43210United States Department of Surgery Division of Surgical OncologyThe Ohio State University Medical CenterColumbusOH 43210United States

Colorectal carcinoma(CRC)is one of the leading causes of cancer-related deaths worldwide,and up to 50%of patients with CRC develop colorectal liver metastases(CRLm).For these patients,surgical resection remains the only opportunity for cure and long-term *** the past few decades,outcomes of patients with metastatic CRC have improved significantly due to advances in systemic therapy,as well as improvements in operative technique and perioperative *** in the modern era of oxaliplatin-and irinotecancontaining regimens has been augmented by the introduction of targeted biologics and immunotherapeutic *** increasing efficacy of contemporary systemic therapies has led to an expansion in the proportion of patients eligible for curative-intent ***,the use of neoadjuvant strategies is becoming progressively more *** patients with CRLm,the primary advantage of neoadjuvant chemotherapy(NCT)is the potential to down-stage metastatic disease in order to facilitate hepatic *** the other hand,the routine use of NCT for patients with resectable metastases remains controversial,especially given the potential risk of inducing chemotherapy-associated liver injury prior to *** guidelines recommend upfront surgery in patients with initially resectable disease and low operative risk,reserving NCT for patients with borderline resectable or unresectable disease and high operative *** undergoing NCT require close monitoring for tumor response and conversion of CRLm to *** light of the growing number of treatment options available to patients with metastatic CRC,it is generally agreed that these patients are best served at tertiary centers with an expert multidisciplinary team.

关键词： Colorectal liver metastases Neoadjuvant chemotherapy Hepatic resection Conversion therapy Chemotherapy-associated liver injury Disappearing liver metastases Future liver remnant Immunotherapy

more accurate reporting of surgical techniques would be SUPER

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Hepatobiliary Surgery and Nutrition 2023年第4期12卷 628-630页

作者： Samantha m.Ruff timothy m.Pawlik Division of Surgical Oncology Department of SurgeryThe Ohio State UniversityWexner Medical CenterColumbusOHUSA

Surgical education entails learning to care for patients in and out of the operating ***,this encompasses everything from the preoperative work-up to managing potential postoperative *** the operating room,surgical technique includes common,widely applicable skills,like how to square a knot,but also the more nuanced anatomical considerations of each operation,intra-operative decision-making,and ways to adapt when faced with the ***,surgical technique was taught through the apprenticeship model with knowledge passed down from attending to trainee and through textbooks written by surgical *** mode of learning/teaching is still the enduring structure of most residency programs.

关键词： Surgical technique reporting guidelines education

Trends in the use of adjuvant therapy for resected intrahepatic cholangiocarcinoma: getting ahead of the data

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Hepatobiliary Surgery and Nutrition 2021年第4期10卷 515-517页

作者： Jordan m.Cloyd timothy m.Pawlik Department of Surgery Division of Surgical OncologyThe Ohio State University Wexner Medical CenterColumbusOHUSA

Intrahepatic cholangiocarcinoma(ICC),the second most common primary liver malignancy,is an aggressive cancer occurring with increasing global *** advances in our understanding of its pathogenesis and molecular underpinnings,diagnostic and staging capabilities,and locoregional and systemic treatment options have occurred over the past several decades(1).

关键词： hepatic adjuvant pathogenesis

Granulite Facies metamorphic Age and Tectonic Implications of BIFs from the Kongling Group in the Northern Huangling Anticline

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Journal of Earth Science 2012年第5期23卷 648-658页

作者：岑洋彭松柏 timothy m Kusky 蒋幸福王璐 Faculty of Earth Sciences China University of Geosciences State Key Laboratory of Geological Processes and mineral Resources China University of Geosciences Three Gorges Research Center for Geo-hazard Ministry of EducationChina University of Geosciences

We report preliminary results of a geochemical study on banded iron formations （BIFs） in the Zhaojiayangpo （赵家阳坡） area from the Kongling （崆岭） Group in the northern Huangling （黄陵） anticline, on the northern margin of the Yangtze craton. The CL （cathodoluminescence） images of zircons mostly have sector zoning, fir-tree zoning and patched zoning, and a few show core-rim tex-tures with rims having patched zoning. The calculated formation temperatures using the Ti-in-zircon thermometer are 660-808 ℃ （714 ℃C in aver-age）, all indicating that the BIFs underwent granulite facies metamorphism. The age of zir-cons with granulite facies metamorphism is 1 990±14 ma by LA-ICP-mS U-Pb dating, indi-cating that there was a significant granulite fa-cies tectonothermal event in the northern Huangling anticline in the Paleoproterozoic, which may be related with tectonic thermal events of the metamorphism caused by the as-sembly of the Columbia supercontinent with South China. moreover, the REE pattern ischaracterized by depletion in LREE while relatively flat in HREE, LaN/YbN=0.26, with a positive Eu anomaly （Eu/Eu^＊---1.59）, which reveals its hydrothermal sedimentation origin and it may have formed in the environment of submarine exhalation.

关键词： Huangling anticline banded iron formation (BIF) zircon LA-ICP-mS U-Pb dating,granulite facies metamorphism Columbia supercontinent.

Twin Earthquakes Devastate Southeast Türkiye and Syria:First Report from the Epicenters

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Journal of Earth Science 2023年第2期34卷 291-296页

作者： timothy m.Kusky Erdin Bozkurt Jiannan meng Lu Wang Badong National Observatory and Research Station for Geohazards Center for Global TectonicsSchool of Earth SciencesChina University of GeosciencesWuhan 430074China Department of Geological Engineering Middle East Technical University06800 AnkaraTürkiye

In early February,2023,southeastern Türkiye and northern Syria were hit by a series of deadly earthquakes(two of them above magnitude 7.5)that are proving to be one of the most significant earthquake disasters of this ***“twin quakes”caused a large number of casualties and property *** of press time,the death toll in Türkiye and Syria has surpassed 51000 and the number of injured has surpassed 120000,with the number affected>13.5 *** toll is constantly rising and the hope of finding more survivors has rapidly *** USGS PAGER(United States Geological Survey,Prompt Assessment of Global Earthquake for Response)service estimates economic losses of 10–100 billion US dollars.

关键词： Earthquake quake southeastern